Technique shields immune system from chemo effects

A research team at the Yale School of Medicine has found a way to save platelets and white blood cells from the adverse effects of chemotherapy.

Led by School of Medicine genetics professor Jun Lu, the team conducted its research at the Yale Stem Cell Center over the past three years. By manipulating a microRNA molecule called miR-150, researchers were able to increase proliferation of white blood cells and platelets in mice, thus strengthening their immune systems, Lu said.

The human blood system is characterized by a rapid turnover of blood cells and platelets, Lu said. During chemotherapy, these cells have a shorter life span because they are being attacked by the drugs. The human body has not evolved to respond efficiently to chemotherapy, and as a result does not produce enough blood cells and platelets, leading to a compromised immune system.

Typically, miR-150 acts like a brake in a car, preventing white blood cells from overproliferation, said study contributor Prem Reddy of The Scripps Research Institute. The microRNA controls cell production by regulating the activity of the Myb gene, which influences the proliferation of white blood cells and platelets. When uncontrolled, the Myb gene can cause cancer by excessive production of these cells, Reddy said. High miR-150 levels lead to the production of fewer cells, he added.

While normal regulation will not harm people with healthy immune systems, these effects can be damaging to chemotherapy patients.

In a normal adult, approximately 10 billion white blood cells must be generated every day to compensate for daily loss, Lu said. For patients undergoing chemotherapy, which kills both cancerous and noncancerous cells, the necessary rate of generation is even higher. If miR-150 is suppressed and Myb levels are allowed to increase, enough cells can be generated to prevent the immune system from being compromised, Reddy said.

Massachusetts Institute of Technology biology professor Phil Sharp, a 1993 recipient of the Nobel Prize in physiology or medicine, said he considers this research “interesting and novel.” Although there are growth factor therapies that regenerate a patient’s immune system, this isolation and targeting of microRNA has not been done in previous studies, he said.

Before the study’s findings are applied in a patient setting, however, Lu’s team will have to replicate these results in humans. They will then have to find or create drugs that will help suppress miR-150 and determine ways to deliver these drugs to “cells of interest” in the body, Lu said. After these steps, they will be able to conduct clinical trials.

If the drug the team finds is already approved by the United States Food and Drug Administration, Lu said, the clinical trial phase may be shorter, as its side effects will already be known.

Sharp said that while it may take years before this technique is used in humans, Lu’s findings show promise.

“It demonstrates one more time that good, basic research not only extends our basic knowledge about the human body, but also paves the way for clinical advances that ultimately benefit the patient,” Reddy said.

Changchun Xiao of The Scripps Research Institute and Haitao Bai of Shanghai First People’s Hospital also contributed to the study.